Cancer breast is the most common malignant tumor in females globally, with newly diagnosed cases 2,088,849 and number of deaths of 626,679 reported by GOBOCAN (2018) and Bray et al., (2018) about half of the world cancer breast cases and the majority of the cancer breast deaths were reported to occur in the developing countries (Torre et al., 2017). In Egypt cancer breast represents 38.8% of newly diagnosed cancer cases among Egyptian females (Ibrahim et al., 2014). Breast cancer etiology and pathogenesis involve genetic, hormonal and other modifying factors. (Sotos et al., 2018) Mechanisms linking inflammatory cytokines and tumour growth and progression have not been established yet as some cytokines (IL2, IL11 and TGF beta) stimulate cancer breast growth and invasion, while others (IL12,IL 18and interferons) inhibit it (Capone et al., 2016). IL-18 has been found to play a dual role in cancer, as it can promote tumor development, progression, migration, invasion, and metastasis. However, it enhances

Background Breast cancer (BC) is the leading cause of cancer death in women worldwide. Most BC studies on candidate microRNAs were tissue specimen based. Recently, there has been a focus on the study of cell‐free circulating miRNAs as promising biomarkers in (BC) diagnosis and prognosis. Therefore, we aimed to investigate the circulating levels of miR‐10b and its target soluble E‐ cadherin as potentially easily accessible biomarkers for breast cancer. Methods Sixty‐one breast cancer patients and forty‐eight age‐ and sex‐matched healthy volunteers serving as a control group were enrolled in the present study. Serum samples were used to assess miRNA10b expression by TaqMan miRNA assay technique. In addition, soluble E‐cadherin expression level in serum was determined using ELISA technique. Result Circulating miR‐10b expression level and serum sE‐cadherin was significantly upregulated in patients with BC compared to controls. Moreover, serum miR‐10b displayed progressive up‐regulation in advanced stages with higher level in metastatic compared to non‐metastatic BC. Additionally, the combined use of both serum miR‐10b and sE‐cadherin revealed the highest sensitivity and specificity for detection of BC metastasis (92.9% and 97.9% respectively) with an area under curve (AUC) of 0.98, 95% CI (0.958–1.00). Conclusion Our data suggest that circulating miR‐10b could be utilized as a potential non‐invasive serum biomarker for diagnosis and prognosis of breast cancer with better performance to predict BC metastasis achieved on measuring it simultaneously with serum sE‐cadherin. Further studies with a large cohort of patients are warranted to validate the serum biomarker for breast cancer management.

Background: Oxidative stress is considered to be involved in the pathophysiology of all cancers. Studies indicated that the levels of oxidative stress markers increased in breast cancer. Trace metals are essential to normal human homeostasis. When present in an abnormal expression, they contribute in many pathological processes. Some trace metals are claimed to be carcinogenic and capable of inducing a toxic effect through the formation of free radicles and acting as cofactors in the oxidative damage of biological macromolecules and DNA. Objective: Our aim was to investigate the serum levels of some trace elements (Copper, Zinc and Cadmium), the total oxidative and antioxidative capacity (TOC and TAC) in patients with breast cancer in comparison to patients with benign breast tumours. Patients and Methods: The present study included 65 females. The participates were divided into 2 main groups: control group which consisted of 20 apparently healthy female; the patient groups which divided into 3 groups: group B included 15 patients with benign breast tumours, group N consisted of 15 newly diagnosed breast cancer patients and group M included 15 patients with metastatic breast cancer. Results: The mean serum levels of Copper, Zinc, and Cadmium were significantly higher in the three patients groups (B, N and M) than the control group. Similarly, serum uric acid (UA) and (TAC) levels showed significant higher level in both breast cancer groups as compared to the benign group. However TOC levels showed only significantly higher level in metastatic group. Conclusions: The present study suggested elevated TAC, UA and TOC in breast cancer patients. The increased levels of trace elements could lead to formation of free radicals or other reactive oxygen species. The serum profile of these trace metals may be helpful in predicting prognosis of breast cancer.

Background: Breast cancer is a disease characterized by progressive genetic abnormalities including mutations in tumor suppressor genes and oncogenes, as well as other chromosomal abnormalities. Protein inhibitor of activated signal transducer and activator of transcription 3 (PIAS3) is a member of the PIAS family of transcriptional modulators; its expression is altered in many cancers. Micro-ribonucleic acid (miRNA)-18a acts as an oncogene by negatively regulating PIAS3 and thus modulating the expression of signal transducer and activator of transcription 3 (STAT3) target genes. The aim of this work is to examine the expression levels of PIAS3 gene and miRNA-18a in breast cancer tissues and nearby non-tumor tissues. The samples of breast cancer and paired samples of noncancerous tissue from the same resected breast were obtained from 25 patients undergoing surgery. Full history taking, complete physical examination, pre-operative fine-needle aspiration cytology or ultrasonic (U/S)-guided core biopsy from the breast mass, final surgical biopsy for pathological examination, and routine laboratory investigations were done. Estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) status were evaluated. Total RNA extraction followed by real-time reverse transcriptionpolymerase chain reaction (RT-PCR) for quantification of PIAS3 mRNA and miRNA-18a expressions was performed. Results: The mean value of PIAS3 mRNA fold expression was significantly lower in the tumor group (5.12 ± 9.85) compared to the normal group (8.38 ± 17.10) (p = 0.040). miRNA-18a fold expression was higher among tumor group (3.5 ± 7.4) than that of normal group (2.5 ± 3), however, it did not reach the level of statistical significance (p = 0.861). miRNA-18a fold expression had negative significant correlation with PIAS3 mRNA fold expression (p = 0.018). A significant association was observed between miRNA-18a expression in breast cancer tissues and the pathological grade of the tumor (p = 0.029). Conclusions: The results of this study showed that PIAS3 mRNA and miRNA-18a might be of importance in breast cancer development and pathogenesis, and this may be reflected on the treatment strategies targeting STAT3 pathway. However, further studies with larger sample size are needed to validate these observations.

Background In recent years, hypermethylation of gene promoters has emerged as one of the fundamental mechanisms for the inactivation of tumor suppressor genes and has a potential role in the early detection of breast cancer. The present study is a case-control study aimed to quantify the methylation levels in the promoters of secretoglobin 3A1 (SCGB3A1), and ataxia-telangiectasia mutated (ATM) genes and evaluate their relation to clinicopathological features of the tumor in a cohort of Egyptian female patients with breast cancer. Methods Genomic deoxyribonucleic acid (DNA) was extracted from 100 tissue samples, 50 breast cancer tissues and 50 adjacent non-cancerous breast tissues, then, it was subjected to bisulfite conversion. The converted DNA was amplified by real-time PCR; then, pyrosequencing was performed to quantify DNA methylation levels in four CpG sites in ATM and SCGB3A1 gene promoters. The methylation data were presented as the percentage of average methylation of all the observed CpG sites and were calculated for each sample and each gene. Results The percentage of DNA methylation of the SCGB3A1 promoter was significantly higher in the tumor group than in the normal group (P= 0.001). However, a non-statistical significance difference was found in the DNA methylation percentage of the ATM promoter in the tumor group compared to the normal group (P = 0.315). The SCGB3A1 promoter methylation frequency was significantly associated with estrogen receptors (ER) and progesterone receptors (PR) positive tumors, lymph node metastasis, and lymphovascular invasion. However, no association was found between ATM methylation status and the different clinicopathological features of the tumor. Conclusions The findings of this work showed that the SCGB3A1 promoter methylation was significantly higher in the tumor group and was significantly associated with different clinicopathologic features in breast cancer. It may be considered as a suitable biomarker for diagnosis and prognosis. However, the promoter methylation levels of the ATM gene in breast cancer cases were unable to distinguish between breast cancer tissues and adjacent normal tissues, and there is no evidence that epigenetic silencing by ATM methylation has a role in breast cancer pathogenesis.